Regulation of SWI/SNF chromatin remodeler composition and function
Active Project Grant Awarded Last action
- Award ID
- R15GM151701
- Recipient
-
University Of Rhode Island UEI CJDNG9D14MW7 Part of State Of Rhode Island
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $455,630
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 77% complete
- Place of performance
- Kingston, RI 02881, USA
Award details come from USAspending.gov.
Description
- Abstract
- The evolutionarily conserved SWI/SNF chromatin remodeler, exists as distinct polymorphic complexes, BAF, pbaf and ncbaf, each with differing subunit composition. Though these complexes share a common biological function of altering chromatin architecture, IT is the unique subunits within each form of SWI/SNF that help define their genomic roles. With the identification of SWI/SNF as a tumor suppressor, a lot of attention has been focused on how loss of subunits leverage the remaining complexes for transcriptional output. However, focusing attention on a normal cell that needs to constantly adjust transcriptional output to respond to a variety of external stimuli, an interesting question remains: how do cells dynamically alter the usage of the various SWI/SNF complexes for gene expression and do they achieve this dynamic usage by changing the amounts of each form of the complex within cells. We have leveraged hypoxia as an environmental stimulus to address this very question. Our preliminary studies show that hypoxic cells retain BAF and ncbaf proteins at levels similar to those in normoxic cells, but decrease levels of pbaf members, while displaying a dependence on BAF for expression of hypoxic genes. The overall goal of this proposal is to gain mechanistic understanding of the dynamic regulation and usage of various forms of SWI/SNF as a response to environmental cues, specifically hypoxic exposure. In aim 1, we will define the composition of the various forms of SWI/SNF, during hypoxic response, with emphasis on how varying levels of oxygen concentration affects SWI/SNF complex levels, using both 2D and 3D cell culture models. In aim 2, we ask how cells use the altered stoichiometry of SWI/SNF forms for regulation of hypoxic gene expression. In aim 3, we seek to define the molecular mechanisms of downregulation of pbaf during hypoxia. Our studies, will cumulatively provide a mechanistic understanding of how cells dynamically utilize the various forms of SWI/SNF to respond to changing environmental signals. Given that many chromatin modifiers exist in a plurality of forms, our studies will help identify mechanisms that may commonly be in play to regulate functions and usage of these important enzyme complexes.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $455,630 |
Quick answers
Who received award R15GM151701?
R15GM151701 was awarded to University Of Rhode Island by National Institute of General Medical Sciences (National Institutes of Health) on July 1, 2024.
How much is award R15GM151701 worth?
$455,630 has been obligated on R15GM151701.
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